The objective of this research is to evaluate the pharmacokinetic importance of the lung in the uptake, metabolism, storage and release of endogenous and exogenous chemicals. Pharmacokinetic data is correlated with toxicological, physiological and biochemical changes induced during the accumulation of chemicals by the lung. These studies make considerable use of the isolated perfused lung (IPL) preparation. The IPL permits examination of the pharmacokinetics of chemicals reaching the lung both from the circulation and inhaled air. Pharmacokinetic models are constructed from the data and related to pulmonary damage resulting from exposure to environmental chemicals. The role of the lung in the whole body distribution of chemicals will be assessed and incorporated into pharmacokinetic models.